Molecule Information
General Information of the Molecule (ID: Mol00120)
| Name |
ATP-binding cassette sub-family C2 (ABCC2)
,Homo sapiens
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| Synonyms |
Canalicular multidrug resistance protein; Canalicular multispecific organic anion transporter 1; Multidrug resistance-associated protein 2; CMOAT; CMOAT1; CMRP; MRP2
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| Molecule Type |
Protein
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| Gene Name |
ABCC2
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| Gene ID | |||||
| Location |
chr10:99782640-99852594[+]
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| Sequence |
MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGYLWLLAPWQLLHVYKSRTKRSS
TTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYS RQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILI FSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVS KFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSG TKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIG YLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGET VNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAIL STKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFS QLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMI SSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLD IMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNIL FGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLD IYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIV EKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAAS ITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETG KVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQR DMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRI VNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMF YVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSW ITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTS EIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGI TCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTII PQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIG QRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMD SDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF Click to Show/Hide
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| 3D-structure |
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| Function |
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates. Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification. Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4. Transports sulfated bile salt such as taurolithocholate sulfate. Transport various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors. Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine.
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| Uniprot ID | |||||
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| Click to Show/Hide the Complete Species Lineage | |||||
Type(s) of Resistant Mechanism of This Molecule
Drug Resistance Data Categorized by Drug
Approved Drug(s)
7 drug(s) in total
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Non-small cell lung cancer [ICD-11: 2C25.Y] | [1] | |||
| Resistant Disease | Non-small cell lung cancer [ICD-11: 2C25.Y] | |||
| Resistant Drug | Cisplatin | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Lung cancer [ICD-11: 2C25] | |||
| The Specified Disease | Lung cancer | |||
| The Studied Tissue | Lung tissue | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.02E-08 Fold-change: 6.65E-02 Z-score: 5.77E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | Caspase-3 signaling pathway | Inhibition | hsa04210 | |
| Cell apoptosis | Inhibition | hsa04210 | ||
| In Vitro Model | A549 cells | Lung | Homo sapiens (Human) | CVCL_0023 |
| A549/DDP cells | Lung | Homo sapiens (Human) | CVCL_0023 | |
| In Vivo Model | BALB/c nude mice xenograft model | Mus musculus | ||
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | ABCC2 knockdown reversed DDP resistance and promoted G1 phase arrest in A549/DDP cells, and PARP and caspase-3 were activated in A549/DDP cells following ABCC2 knockdown. In vivo, ABCC2 knockdown enhanced the cytotoxicity of DDP to subcutaneous A549 t. | |||
| Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] | [2] | |||
| Resistant Disease | Oral squamous cell carcinoma [ICD-11: 2B6E.0] | |||
| Resistant Drug | Cisplatin | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | Caspase-3 signaling pathway | Activation | hsa04210 | |
| In Vitro Model | CAL27 cells | Oral | Homo sapiens (Human) | CVCL_1107 |
| HSC3 cells | Tongue | Homo sapiens (Human) | CVCL_1288 | |
| HaCaT cells | Tongue | Homo sapiens (Human) | CVCL_0038 | |
| OSCC3 cells | Tongue | Homo sapiens (Human) | CVCL_L894 | |
| SCC4 cells | Tongue | Homo sapiens (Human) | CVCL_1684 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of LncRNA ANRIL in tumour cells. ANRIL knockdown overcomes Mk-induced cisplatin resistance via activation of caspase-3-dependent apoptosis. Overexpression of LncRNA ANRIL promots the up-regulation of ABC family proteins MRP1 and ABCC2, which ultimately results in tumour cell resistance to cisplatin. | |||
| Disease Class: Prostate cancer [ICD-11: 2C82.0] | [3] | |||
| Resistant Disease | Prostate cancer [ICD-11: 2C82.0] | |||
| Resistant Drug | Cisplatin | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | PC3 cells | Prostate | Homo sapiens (Human) | CVCL_0035 |
| 22RV1 cells | Prostate | Homo sapiens (Human) | CVCL_1045 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr. | |||
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Ovarian cancer [ICD-11: 2C73.0] | [4] | |||
| Sensitive Disease | Ovarian cancer [ICD-11: 2C73.0] | |||
| Sensitive Drug | Cisplatin | |||
| Molecule Alteration | Expression | Down-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | SkOV3 cells | Ovary | Homo sapiens (Human) | CVCL_0532 |
| OVCAR3 cells | Ovary | Homo sapiens (Human) | CVCL_0465 | |
| OVCAR3/CDDP cells | Ovary | Homo sapiens (Human) | CVCL_0465 | |
| SkOV3/CDDP cells | Ovary | Homo sapiens (Human) | CVCL_D622 | |
| In Vivo Model | Mouse xenograft model | Mus musculus | ||
| Experiment for Molecule Alteration |
Luciferase assay; Western blot analysis; Immunohistochemical staining assay | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | miR490-3p sensitizes ovarian cancer cells to cisplatin by directly targeting ABCC2. miR490-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ABCC2 expression. | |||
| Disease Class: Nasopharyngeal carcinoma [ICD-11: 2B6B.0] | [5] | |||
| Sensitive Disease | Nasopharyngeal carcinoma [ICD-11: 2B6B.0] | |||
| Sensitive Drug | Cisplatin | |||
| Molecule Alteration | Expression | Down-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | 5-8F cells | Nasopharynx | Homo sapiens (Human) | CVCL_C528 |
| CNE2 cells | Nasopharynx | Homo sapiens (Human) | CVCL_6889 | |
| CNE1 cells | Throat | Homo sapiens (Human) | CVCL_6888 | |
| HONE1 cells | Throat | Homo sapiens (Human) | CVCL_8706 | |
| 6-10B cells | Nasopharynx | Homo sapiens (Human) | CVCL_C529 | |
| In Vivo Model | BALB/c nude mice xenograft model | Mus musculus | ||
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | Lentiviral vectors were constructed to allow an efficient expression of anti-ABCC2 siRNA. The accumulation of intracellular cisplatin in these CNE2 cell clones with reduced expression of ABCC2 increased markedly, accompanied by increased sensitivity against cisplatin. lentivirus-mediated RNAi silencing targeting ABCC2 might reverse the ABCC2-related drug resistance of NPC cell line CNE2 against cisplatin. | |||
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Prostate cancer [ICD-11: 2C82.0] | [3] | |||
| Resistant Disease | Prostate cancer [ICD-11: 2C82.0] | |||
| Resistant Drug | Doxorubicin | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | PC3 cells | Prostate | Homo sapiens (Human) | CVCL_0035 |
| 22RV1 cells | Prostate | Homo sapiens (Human) | CVCL_1045 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | However, higher concentrations of probenecid (500 uM) failed to demonstrate a chemosensitizing effect. Consistent with this lower chemosensitizing efficacy in higher-concentration probenecid treatment, we observed that the expression of ABCG2, a drug-efflux transporter, increased in a dose-dependent manner following probenecid treatment. Thus, probenecid could enhance the chemosensitivity of 3D-cultured prostate cancer cells, but not at higher concentr. | |||
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] | [6] | |||
| Resistant Disease | Chronic myeloid leukemia [ICD-11: 2A20.0] | |||
| Resistant Drug | Imatinib | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| In Vitro Model | K562 cells | Blood | Homo sapiens (Human) | CVCL_0004 |
| Experiment for Molecule Alteration |
Western blot analysis; Luciferase reporter assay | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | ABCC2 was a downstream target of miR205-5p, overexpression of miR205-5p suppressed the expression of ABCC2 in k562-R cells. SNHG5 promotes imatinib resistance through upregulating ABCC2. SNHG5 promotes imatinib resistance in CML via acting as a competing endogenous RNA against miR205-5p. | |||
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Ovarian cancer [ICD-11: 2C73.0] | [7] | |||
| Resistant Disease | Ovarian cancer [ICD-11: 2C73.0] | |||
| Resistant Drug | Ketoprofen | |||
| Molecule Alteration | Function | Inhibition |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | SW48 cells | Colon | Homo sapiens (Human) | CVCL_1724 |
| A2780/RCIS cells | Ovary | Homo sapiens (Human) | N.A. | |
| Experiment for Molecule Alteration |
Flow cytometric efflux assay | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | A new series of quinoline analogs of ketoprofen was designed and synthesized as multidrug resistance protein 2 (MRP2) inhibitors using ketoprofen as the lead compounds. | |||
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Colorectal carcinoma [ICD-11: 2B91.3] | [8] | |||
| Sensitive Disease | Colorectal carcinoma [ICD-11: 2B91.3] | |||
| Sensitive Drug | Oxaliplatin | |||
| Molecule Alteration | Expression | Down-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | Cell apoptosis | Activation | hsa04210 | |
| In Vitro Model | HCT116 cells | Colon | Homo sapiens (Human) | CVCL_0291 |
| HCT-8 cells | Colon | Homo sapiens (Human) | CVCL_2478 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells, miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. | |||
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Prostate cancer [ICD-11: 2C82.0] | [3] | |||
| Sensitive Disease | Prostate cancer [ICD-11: 2C82.0] | |||
| Sensitive Drug | Probenecid | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | Cell autophagy | Inhibition | hsa04140 | |
| Cell cytotoxicity | Activation | hsa04650 | ||
| In Vitro Model | PC3 cells | Prostate | Homo sapiens (Human) | CVCL_0035 |
| 22RV1 cells | Prostate | Homo sapiens (Human) | CVCL_1045 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | However, probenecid only weakly inhibits ABCG2. Thus, probenecid enhanced the efficacy of anticancer drugs against 22Rv1 spheroids by inhibiting drug resistance-related transporters such as MRP; at high probenecid concentrations, the chemosensitization effect may be reduced owing to promotion of alternate drug excretion pathways via upregulated ABCG2 expression. | |||
| Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Colorectal carcinoma [ICD-11: 2B91.3] | [8] | |||
| Sensitive Disease | Colorectal carcinoma [ICD-11: 2B91.3] | |||
| Sensitive Drug | Vincristine | |||
| Molecule Alteration | Expression | Down-regulation |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | Cell apoptosis | Activation | hsa04210 | |
| In Vitro Model | HCT116 cells | Colon | Homo sapiens (Human) | CVCL_0291 |
| HCT-8 cells | Colon | Homo sapiens (Human) | CVCL_2478 | |
| Experiment for Molecule Alteration |
Western blot analysis | |||
| Experiment for Drug Resistance |
MTT assay | |||
| Mechanism Description | MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells, miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. | |||
Clinical Trial Drug(s)
1 drug(s) in total
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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| Disease Class: Melanoma [ICD-11: 2C30.0] | [9] | |||
| Resistant Disease | Melanoma [ICD-11: 2C30.0] | |||
| Resistant Drug | Vemurafenib/Cobimetinib | |||
| Molecule Alteration | Expression | Down-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | Hs294T R cells | Skin | Homo sapiens (Human) | CVCL_E3AI |
| Experiment for Molecule Alteration |
Western blot assay; qRT-PCR | |||
| Experiment for Drug Resistance |
XTT assay | |||
| Mechanism Description | ABC transporters and CYP1A1 protein level was also upregulated in resistant cells. Moreover, the elevated levels of ABCA1, ABCC2 and ABCG2 were here shown for the first time in BRAFi/MEKi resistant cells. | |||
| Disease Class: Melanoma [ICD-11: 2C30.0] | [9] | |||
| Resistant Disease | Melanoma [ICD-11: 2C30.0] | |||
| Resistant Drug | Vemurafenib/Cobimetinib | |||
| Molecule Alteration | Expression | Up-regulation |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| In Vitro Model | WM9 R cells | melanoma | Homo sapiens (Human) | CVCL_E3AH |
| Experiment for Molecule Alteration |
Western blot assay; qRT-PCR | |||
| Experiment for Drug Resistance |
XTT assay | |||
| Mechanism Description | ABC transporters and CYP1A1 protein level was also upregulated in resistant cells. Moreover, the elevated levels of ABCA1, ABCC2 and ABCG2 were here shown for the first time in BRAFi/MEKi resistant cells. | |||
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
| Differential expression of molecule in resistant diseases | ||
| The Studied Tissue | Whole blood | |
| The Specified Disease | Myelofibrosis | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 5.87E-01; Fold-change: -2.27E-02; Z-score: -1.39E-01 | |
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Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
| The Studied Tissue | Whole blood | |
| The Specified Disease | Polycythemia vera | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 5.58E-03; Fold-change: 9.73E-02; Z-score: 5.83E-01 | |
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Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
| Differential expression of molecule in resistant diseases | ||
| The Studied Tissue | Oral tissue | |
| The Specified Disease | Oral squamous cell carcinoma | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 2.89E-03; Fold-change: -2.40E-01; Z-score: -9.52E-01 | |
| The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 6.28E-01; Fold-change: -6.84E-02; Z-score: -2.77E-01 | |
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Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
| Differential expression of molecule in resistant diseases | ||
| The Studied Tissue | Lung | |
| The Specified Disease | Lung cancer | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.02E-08; Fold-change: -5.12E-02; Z-score: -2.22E-01 | |
| The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 5.76E-09; Fold-change: 3.50E-03; Z-score: 1.38E-02 | |
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Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
| Differential expression of molecule in resistant diseases | ||
| The Studied Tissue | Ovary | |
| The Specified Disease | Ovarian cancer | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 9.91E-01; Fold-change: -4.05E-02; Z-score: -1.15E-01 | |
| The Expression Level of Disease Section Compare with the Adjacent Tissue | p-value: 9.62E-01; Fold-change: -2.75E-02; Z-score: -9.63E-02 | |
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Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
| Differential expression of molecule in resistant diseases | ||
| The Studied Tissue | Prostate | |
| The Specified Disease | Prostate cancer | |
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.58E-01; Fold-change: -4.23E-01; Z-score: -7.28E-01 | |
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Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
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| Disease-specific Molecule Abundances |
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Click to View the Clearer Original Diagram |
Tissue-specific Molecule Abundances in Healthy Individuals
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References
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